Collagen metabolism in folic acid deficiency.

I . The effect of folic acid deficiency on collagen formation, with respect to the level of collagen-protein synthesis and the extent of collagen-proline hydroxylation, has been studied. A folic acid-free diet containing 10 g sulphasuxidine/kg was used to induce folate deficiency in young male rats. Animals were judged folic acid-deficient on the grounds of retardation of growth, characteristic haematological changes and the urinary excretion of formimino-L-glutamic acid. 2. From isotope incorporation studies it was found that folic acid deficiency caused a marked impairment in collagen synthesis. It was shown, however, from the use of pair-fed control animals, that this was due in part to a reduced food intake accompanying the vitamin deficiency. The further reduction in synthesis in addition to that attributable to inanition was considered to arise from an involvement of folk acid in general protein synthesis, since it was found that the synthesis of elastin and non-collagenous skin proteins was similarly impaired. 3. Reduced synthesis of collagen was not considered attributable to lack of hydroxylation of peptidyl proline that may occur in ascorbic acid deficiency. Hydroxylation of collagenand elastin-proline was only very slightly impaired in folic acid deficiency. It was concluded that, at least when ascorbic acid is present, folk acid is not directly essential for the hydroxylation, in vivo, of peptidyl proline. The results support the view that ascorbic acid participates direct, in vivo, in this hydroxylation rather than indirect by simply maintaining an adequate level of reduced folates. They do not, however, exclude the possibility, arising from the known ability of tetrahydrofolate to participate in the hydroxylation of collagen proline in vitro, that when both ascorbate and folate are present, the latter may, in some measure, share in the role of reducing agent in the hydroxylation of peptidyl proline in vivo.